The two dopamine receptor hypothesis provides new pharmacological approaches for innovative therapy of disease states. This project investigates the biochemistry of the D-1 and the D-2 dopamine receptors. the knowledge gained about the D-1 and the D-2 receptors may facilitate the development of drugs effective in the treatment of Parkinson's disease, endocrine disorders, psychiatric disorders, hypertension and antiemetics in cancer chemotherapy. The pharmacology of the D-1 and the D-2 receptors was investigated in the current fiscal year. This endeavour led to the identification of (+)-bulbocapnine as an antagonist of the D-2 receptor devoid of activity upon the D-2 receptor and a clarification of the structural basis for the selective D-2 agonist activity of LY 141865. Furthermore, the N-propyl effect was investigated in both the aporphine and 2-amino tetralin series of dopamine agonists. These studies will permit the development of more selective agonists and antagonists of either category of dopamine receptor. The biochemical consequences of stimulating the D-2 receptor in the intermediate lobe (IL) of the rat pituitary gland were investigated. The results of this project show that stimulation of this D-2 receptor controls the sensitivity of the D-2 receptor, the size of the IL and the expression of the gene(s) regulating the expression of the proopiomelanocortin gene. Furthermore, these studies provide additional roles for the neurotransmitter, dopamine, within the IL. The involvement of cAMP in the functioning of the IL was investigated in the current fiscal year. These studies identified forskolin as a useful tool for investigating cAMP metabolism in the IL. The advantage of forskolin over other stimultory agents is that forskolin is rapid acting and displays the same potency upon cAMP accumulation and hormone release. This property facilitates the design of experiments to determine the role of cAMP in hormone release. Studies of cAMP-dependent protein kinase and the drug-induced changes in its activity were also initiated.